G. B. Postnikova* and E. A. Shekhovtsova

Received April 24, 2017; Revision received September 15, 2017
In this review, we shortly summarize the data of our studies (and also
corresponding studies of other authors) on the new mechanism of
myoglobin (Mb) deoxygenation in a cell, according to which Mb acts as
an oxygen transporter, and its affinity for the ligand, like in other
transporting proteins, is regulated by the interaction with the target,
in our case, mitochondria (Mch). We firstly found that contrary to
previously formulated and commonly accepted concepts, oxymyoglobin
(MbO2) deoxygenation occurs only via interaction of the
protein with respiring mitochondria (low pO2 values
are necessary but not sufficient for this process to proceed). Detailed
studies of the mechanism of Mb–Mch interaction by various
physicochemical methods using natural and artificial bilayer
phospholipid membranes showed that: (i) the rate of MbO2
deoxygenation in the presence of respiring Mch fully coincides with the
rate of O2 uptake by mitochondria from a solution
irrespectively of their state (native coupled, freshly frozen, or
FCCP-uncoupled), i.e. it is determined by the respiratory activity of
Mch; (ii) Mb nonspecifically binds to membrane phospholipids of the
outer mitochondrial membrane, while any Mb-specific protein or
phospholipid sites on it are lacking; (iii) oxygen uptake by Mch from a
solution and the uptake of Mb-bound oxygen are two different processes,
as their rates are differently affected by proteins (e.g. lysozyme)
that compete with MbO2 for binding to the mitochondrial
membrane; (iv) electrostatic forces significantly contribute to the
Mb–membrane interactions; the dependence of these interactions on
ionic strength is provided by the local electrostatic interactions
between anionic groups of phospholipids (the heads) and invariant Lys
and Arg residues near the Mb heme pocket; (v) interactions of Mb with
phospholipid membranes promote conformational changes in the protein,
primarily in its heme pocket, without significant alterations in the
protein secondary and tertiary structures; and (vi) Mb–membrane
interactions lead to decrease in the affinity of myoglobin for
O2, which could be monitored by the increase in the
MbO2 autooxidation rate under aerobic conditions and under
anaerobic ones, by the shift in the MbO2/Mb(2) equilibrium
towards the ligand-free protein. The decrease in the affinity of Mb for
the ligand should facilitate O2 dissociation from
MbO2 at physiological pO2 values in cells.
KEY WORDS: myoglobin, mitochondria, spatial structure,
deoxygenation mechanism